Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia
Abstract Schizophrenia may represent a trade-off in the evolution of human-specific ontogenetic mechanisms that guide neurodevelopment. Human Accelerated Regions (HARs) are evolutionary markers functioning as neurodevelopmental transcription enhancers that have been associated with brain configurati...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05356-2 |
| _version_ | 1797557210134347776 |
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| author | Maria Guardiola-Ripoll Carmen Almodóvar-Payá Angelo Arias-Magnasco Mariona Latorre-Guardia Sergi Papiol Erick J. Canales-Rodríguez María Ángeles García-León Paola Fuentes-Claramonte Josep Salavert Josep Tristany Llanos Torres Elena Rodríguez-Cano Raymond Salvador Edith Pomarol-Clotet Mar Fatjó-Vilas |
| author_facet | Maria Guardiola-Ripoll Carmen Almodóvar-Payá Angelo Arias-Magnasco Mariona Latorre-Guardia Sergi Papiol Erick J. Canales-Rodríguez María Ángeles García-León Paola Fuentes-Claramonte Josep Salavert Josep Tristany Llanos Torres Elena Rodríguez-Cano Raymond Salvador Edith Pomarol-Clotet Mar Fatjó-Vilas |
| author_sort | Maria Guardiola-Ripoll |
| collection | DOAJ |
| description | Abstract Schizophrenia may represent a trade-off in the evolution of human-specific ontogenetic mechanisms that guide neurodevelopment. Human Accelerated Regions (HARs) are evolutionary markers functioning as neurodevelopmental transcription enhancers that have been associated with brain configuration, neural information processing, and schizophrenia risk. Here, we have investigated the influence of HARs’ polygenic load on neuroanatomical measures through a case-control approach (128 patients with schizophrenia and 115 controls). To this end, we have calculated the global schizophrenia Polygenic Risk Score (Global PRSSZ) and that specific to HARs (HARs PRSSZ). We have also estimated the polygenic burden restricted to the HARs linked to transcriptional regulatory elements active in the foetal brain (FB-HARs PRSSZ) and the adult brain (AB-HARs PRSSZ). We have explored the main effects of the PRSs and the PRSs x diagnosis interactions on brain regional cortical thickness (CT) and surface area (SA). The results indicate that a higher FB-HARs PRSSZ is associated with patients’ lower SA in the lateral orbitofrontal cortex, the superior temporal cortex, the pars triangularis and the paracentral lobule. While noHARs-derived PRSs show an effect on the risk, our neuroanatomical findings suggest that the human-specific transcriptional regulation during the prenatal period underlies SA variability, highlighting the role of these evolutionary markers in the schizophrenia genomic architecture. |
| first_indexed | 2024-03-10T17:14:07Z |
| format | Article |
| id | doaj.art-65dda727008240329f9f7fc26b35ae4a |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:14:07Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-65dda727008240329f9f7fc26b35ae4a2023-11-20T10:33:24ZengNature PortfolioCommunications Biology2399-36422023-10-016111010.1038/s42003-023-05356-2Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophreniaMaria Guardiola-Ripoll0Carmen Almodóvar-Payá1Angelo Arias-Magnasco2Mariona Latorre-Guardia3Sergi Papiol4Erick J. Canales-Rodríguez5María Ángeles García-León6Paola Fuentes-Claramonte7Josep Salavert8Josep Tristany9Llanos Torres10Elena Rodríguez-Cano11Raymond Salvador12Edith Pomarol-Clotet13Mar Fatjó-Vilas14FIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationCIBERSAM (Biomedical Research Network in Mental Health; Instituto de Salud Carlos III)CIBERSAM (Biomedical Research Network in Mental Health; Instituto de Salud Carlos III)FIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationHospital Sant Rafael, Germanes HospitalàriesHospital Sagrat Cor, Germanes HospitalàriesHospital Mare de Déu de la Mercè, Germanes HospitalàriesFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationFIDMAG Germanes Hospitalàries Research FoundationAbstract Schizophrenia may represent a trade-off in the evolution of human-specific ontogenetic mechanisms that guide neurodevelopment. Human Accelerated Regions (HARs) are evolutionary markers functioning as neurodevelopmental transcription enhancers that have been associated with brain configuration, neural information processing, and schizophrenia risk. Here, we have investigated the influence of HARs’ polygenic load on neuroanatomical measures through a case-control approach (128 patients with schizophrenia and 115 controls). To this end, we have calculated the global schizophrenia Polygenic Risk Score (Global PRSSZ) and that specific to HARs (HARs PRSSZ). We have also estimated the polygenic burden restricted to the HARs linked to transcriptional regulatory elements active in the foetal brain (FB-HARs PRSSZ) and the adult brain (AB-HARs PRSSZ). We have explored the main effects of the PRSs and the PRSs x diagnosis interactions on brain regional cortical thickness (CT) and surface area (SA). The results indicate that a higher FB-HARs PRSSZ is associated with patients’ lower SA in the lateral orbitofrontal cortex, the superior temporal cortex, the pars triangularis and the paracentral lobule. While noHARs-derived PRSs show an effect on the risk, our neuroanatomical findings suggest that the human-specific transcriptional regulation during the prenatal period underlies SA variability, highlighting the role of these evolutionary markers in the schizophrenia genomic architecture.https://doi.org/10.1038/s42003-023-05356-2 |
| spellingShingle | Maria Guardiola-Ripoll Carmen Almodóvar-Payá Angelo Arias-Magnasco Mariona Latorre-Guardia Sergi Papiol Erick J. Canales-Rodríguez María Ángeles García-León Paola Fuentes-Claramonte Josep Salavert Josep Tristany Llanos Torres Elena Rodríguez-Cano Raymond Salvador Edith Pomarol-Clotet Mar Fatjó-Vilas Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia Communications Biology |
| title | Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia |
| title_full | Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia |
| title_fullStr | Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia |
| title_full_unstemmed | Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia |
| title_short | Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia |
| title_sort | human specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia |
| url | https://doi.org/10.1038/s42003-023-05356-2 |
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